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A series of controlled experiments was carried out on rats to study the effects on the kidneys of the repeated administration of small doses of cadmium for periods of up to 12 months. Renal lesions consisting essentially of tubular atrophy and interstitial fibrosis were produced, and the evidence that these lesions were due solely to cadmium is discussed. No similar lesions occurred in a series of control animals, litter mates of the experimental animals. The lesions were shown to be reproducible in two prolonged experiments on two strains of rats. The relationship between the lesions and the concentration of cadmium in the tissues of the rats is discussed and a comparison is made with tissues from human cases of chronic cadmium poisoning. It is of interest that the cadmium concentration of human tissues and rat experimental tissue is of the same order of magnitude. Animals in which the administration of cadmium was discontinued after five months of the experiment had developed as severe lesions seven months later as those animals which had received cadmium for 12 months. It has been shown previously that the first sign of chronic cadmium poisoning can occur in man for the first time many years after the last exposure, and that the disease once established in man is progressive despite the absence of further exposure.Emphysema and proteinuria have been described in men exposed to cadmium oxide as either dust or freshly formed fume (Friberg, 1948; Bonnell, 1955). The significance of the proteinuria and its relationship to progressive renal damage has been discussed by Bonnell, Kazantzis, and King (1959).Because the evidence that progressive renal damage occurred in men suffering from chronic cadmium poisoning was incomplete, experiments were carried out to study the effect of repeated small doses of cadmium on the kidneys of rats. These experiments are described here, together with a review of the literature involving animal experiments with cadmium. Review of the LiteratureThe earliest work on the toxic effects of cadmium in animals was published by Marme in 1867. He determined the lethal dose of 14 cadmium compounds on dogs, cats, rabbits, and pigeons. The cadmium was administered intravenously, subcutaneously, and orally. He found that the lethal dose for dogs was 30 mg. intravenously and 60-90 mg. subcutaneously. The lethal dose for rabbits was 300-600 mg. by mouth. Small doses of cadmium salts were found to produce chronic effects 6 4 but the actual doses were not mentioned. At necropsy these animals were found to have infarction of the lungs with subpleural haemorrhages, fatty degeneration of the liver and heart, and a diffuse inflammation of the kidneys. The excretion of cadmium was found to be slow and to occur mainly in the urine. The effect of cadmium on the kidneys was studied by Severi in 1896. Ten milligrammes of cadmium as a 1 % solution of cadmium chloride were injected subcutaneously in rabbits and dogs first daily and then on alternate days. The macroscopic and microscopic appearances of the ...